Teneligliptin (MP513; trade name Tenelia in Japan) is a novel, potent, orally bioavailable and long-lasting dipeptidyl peptidase-4 (DPP-4) inhibitor; it competitively inhibited human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50 values of approximately 1 nM. Chronic teneligliptin treatment at doses between 0.1 and 3.0 µmol/L does not reduce cell viability of HUVECs, but decreases HG-stress markers and increases heme oxygenase-1 (HMOX1) gene expression in HUVEC cells incubated under hyperglycemia. Teneligliptin is an approved drug for the treatment of type 2 diabetes mellitus in Japan.

Physicochemical Properties

Molecular Formula	C22H30N6OS
Molecular Weight	426.58
Exact Mass	426.22
CAS #	760937-92-6
Related CAS #	Teneligliptin hydrobromide;906093-29-6;Teneligliptin hydrobromide hydrate;1572583-29-9;Teneligliptin-d8;1391012-95-5;Teneligliptin-d4
PubChem CID	11949652
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	663.4±55.0 °C at 760 mmHg
Flash Point	355.0±31.5 °C
Vapour Pressure	0.0±2.0 mmHg at 25°C
Index of Refraction	1.721
LogP	1.15
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	30
Complexity	594
Defined Atom Stereocenter Count	2
SMILES	O=C([C@H]1NC[C@@H](N2CCN(C3=CC(C)=NN3C4=CC=CC=C4)CC2)C1)N5CSCC5
InChi Key	WGRQANOPCQRCME-PMACEKPBSA-N
InChi Code	InChI=1S/C22H30N6OS/c1-17-13-21(28(24-17)18-5-3-2-4-6-18)26-9-7-25(8-10-26)19-14-20(23-15-19)22(29)27-11-12-30-16-27/h2-6,13,19-20,23H,7-12,14-16H2,1H3/t19-,20-/m0/s1
Chemical Name	[(2S,4S)-4-[4-(5-methyl-2-phenylpyrazol-3-yl)piperazin-1-yl]pyrrolidin-2-yl]-(1,3-thiazolidin-3-yl)methanone
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	All of these DPP-4 enzymes are inhibited by teneligliptin (MP-513) in a concentration-dependent manner. Teneligliptin (MP-513) has an IC50 of 0.889, 1.75, and 1.35 nM against rhDPP-4, human plasma, and rat plasma, respectively. Teneligliptin (MP-513) was used as the enzyme source and Gly-Pro-MCA as the substrate in an investigation of the kinetics of enzyme inhibition. Teneligliptin (MP-513) inhibits DPP-4 in a substrate-competitive manner, according to plots based on the Michaelis-Menten equation; the residual sums of squares for the competitive and noncompetitive models were 0.162 and 0.192, respectively. The values of Ki, Km, and Vmax are 6.06 nmol/min, 24 μM, and 0.406 nM, respectively. With an IC50 of 2.92 nM, teneligliptin (MP-513) inhibits the breakdown of GLP-1(7-36)amide[1].
ln Vivo	Teneligliptin (MP-513) has an ED50 of 0.41 mg/kg and can inhibit plasma DPP-4 when given orally to Wistar rats. Even 24 hours after the dose of teneligliptin (MP-513) there was still suppression of plasma DPP-4. Teneligliptin (MP-513) at ≥0.1 mg/kg maximally enhanced plasma glucagon-like peptide-1 and insulin levels and decreased blood glucose excursions in Zucker adipose rats, according to an oral carbohydrate loading test. Within 12 hours of ingesting a dose of 1 mg/kg, this effect is seen. Additionally, triglyceride and free fatty acid excursions were decreased by teneligliptin (MP-513) at a dose of 1 mg/kg in an oral fat loading test conducted on Zucker adipose rats. Teneligliptin (MP-513) was administered twice a week for two weeks in Zucker fatty rats. This treatment decreased plasma triglyceride and free fatty acid levels while the animals were not fasting. It also decreased glucose excursions in an oral carbohydrate loading test. Rat plasma DPP-4 is inhibited by oral treatment of Teneligliptin (MP-513) in a dose-dependent manner. Teneligliptin (MP-513) was shown to have an ED50 value of 0.41 mg/kg, whereas sitagliptin and vildagliptin had ED50 values of 27.3 and 12.8 mg/kg, respectively[1]. Teneligliptin (MP-513) is associated with the downregulation of hepatic lipogenesis-related genes brought on by AMPK activation, which enhances the histological appearance of the liver and lowers intrahepatic triglyceride levels in NAFLD model mice [2].
References	[1]. A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol. 2012 Dec 5;696(1-3):194-202. [2]. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice. Int J Mol Sci. 2015 Dec 8;16(12):29207-18.
Additional Infomation	Teneligliptin is an amino acid amide. Teneligliptin has been investigated for the treatment of Type 2 Diabetes Mellitus. Teneligliptin is a long-acting, orally bioavailable, pyrrolidine-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Teneligliptin may also reduce plasma triglyceride levels through a sustained increase in GLP-1 levels.

Solubility Data

Solubility (In Vitro)

DMSO : ~33.33 mg/mL (~78.13 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3442 mL	11.7211 mL	23.4423 mL
	5 mM	0.4688 mL	2.3442 mL	4.6885 mL
	10 mM	0.2344 mL	1.1721 mL	2.3442 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.